Clinical and Molecular Characterization of Children with Neonatal Diabetes: Experience from Bangladesh.

Neonatal diabetes mellitus (NDM) is a rare monogenic form of diabetes presenting before six months of age which can be permanent (PNDM) or transient (TNDM). In rare cases, NDM can be diagnosed between 6 and 12 months of age. Whilst TNDM is commonly associated with chromosome 6q24 methylation defects, the commonest causes of PNDM are KCNJ11 and ABCC8 gene mutations. This observational study's aim was to assess the clinical features and genetic aetiologies in patients with NDM diagnosed in Bangladesh. The clinical characteristics of 28 patients who presented with NDM from 2001 to 2018 in the in the department of Neonatology and Paediatrics, BIRDEM, Dhaka, Bangladesh were studied. Mutation analyses were carried out by DNA sequencing at Peninsula Molecular Genetics Laboratory, Exeter, UK. Thirteen patients were from 11 consanguineous families. Comprehensive genetic testing was performed on 24 patients. Out of the 28 patients studied, 18(64.0%) had PNDM, 7(25.0%) had TNDM and for 3 the subtype was not known. Causative mutations were detected in 22 of the 24(92.0%) who underwent genetic testing. This included 15 PNDM patients (ABCC8 31.0%, KCNJ11 25.0%, EIF2AK3 19.0%, INS 6.0%) and 7 TNDM patients (6q24 43.0%, ABCC8 29.0%, KCNJ11 14.0%, INS 14.0%). Among consanguineous families, mutations in the ABCC8 gene and E1F2AK3 were common. The median age at diabetes presentation was 80 days (3-210 days), median birth weight was 2250g (1000-3700g), mean gestational age 37.15±1.91 weeks (32-40 weeks). The mean blood glucose at presentation was 29.30±11.73mmol/L (14.0-61mmol/L) with 11 patients (39.0%) presenting with diabetic ketoacidosis. Outcome was good in majority of patents except those with Wolcott-Rallison syndrome due to homozygous EIF2AK3 mutation. All patients with KCNJ11 or ABCC8 NDM were transferred from insulin to sulphonylurea except one. Genetic testing identified mutations in 79.0% (22/28) of this study's NDM cohort. An early genetic diagnosis is essential for patients' clinical management and informing parents on recurrence risk.